We are evaluating the use of monoclonal antibodies (MoAbs) as carriers for cytotoxic agents and radioisotopes, to increase both the selectivity of the agents for cancer therapy and the sensitivity of radiodetection of occult tumor. Several immunoconjugates, composed of A chain of abrin toxin or diphtheria toxin and monoclonal antibodies, (i) D3, to the guinea pig L10 hepatocarcinoma, (ii) 9.2.27 to human melanoma, and (iii) human squamous carcinoma, were shown to retain antigen specificity. The therapeutic effect of D3-A/abrin conjugate was assayed and was capable of inhibiting the tumor growth of primary tumor and delaying or abolishing tumor metastases to lymph nodes. Long-term remission was induced in some tumor-bearers. We have also established two human tumor xenografts in nude mice which will provide models for testing the therapeutic activity of immunoconjugate against human tumor cells. In contrast to the D3 system, the 9.2.27 antimelanoma antibody could inhibit tumor growth in nude mice in unconjugated form, presumably through interaction with effector cells. To study antibody distribution in tumor-bearing animals, MoAb (9.2.27 and D3) were labeled with I-125. Both radioactive MoAb were selectively localized in primary tumors. In addition, I-125-D3 was capable of reaching metastatic tumor in lymph nodes. These studies indicated these MoAb have promising potential for early detection of occult tumor and for selective targeting of therapeutic agents.